DESCRIPTION: The proposed research will explore potential roles of serotonin (5-HT) in the reduction of rat feeding behavior by cocaine- and amphetamine-regulated transcript (CART). Preliminary work from this laboratory extends reports of anorectic responses to intracerebroventricularly administered CART peptides, showing that CART reduces licking behavior, produces serotonin syndrome-like motor signs, and likely exerts these actions at tissues surrounding the fourth ventricle (4V). The specific aims of this proposal are to assess the role of 5-HT in effects of 4V CART on liquid food intake and ingestion patterns, postural motor function, and genomic expression. The strategy will be to abolish 5-HT neurotransmission by selectively lesioning hindbrain serotonergic neurons, or blocking activity at 5-HT2C receptors, and then to examine the effects of 4V CART on intake of a nutritionally complete liquid diet under ad libitum and food deprivation feeding paradigms. Examining mechanisms underlying anorectic and other behavioral actions of CART will contribute to a more complete understanding of the controls of food intake, and may aid in the evaluation of CART as a treatment for obesity.